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Cancer cells have a variety of interactions with neighboring connective tissue, and this activity primarily involves fibroblasts. Co-culture of fibroblasts derived from human skin with cancer cells results in the conversion of fibroblasts into cancer-associated fibroblasts, which are known to support tumor growth and invasiveness. To evaluate the effect of radiation on tumor-fibroblast interactions, the present study co-cultivated fibroblasts from pre-irradiated and non-irradiated human skin with FaDu head and neck squamous cell carcinoma cells for 3 days. Subsequently, cells were analyzed for tumor viability, apoptosis, and secretion of interleukin (IL)-6 and -8 by performing an MTT assay, Annexin V-propidium iodide test and enzyme-linked immunosorbent assay, respectively. Co-culture of FaDu cells with pre-irradiated fibroblasts resulted in a significant decrease in tumor viability, a notable increase in apoptosis and significantly lower levels of IL-8 compared with FaDu cells cultured with non-irradiated fibroblasts. Therefore, we propose that pre-irradiation changes the properties of fibroblasts and their effects on co-cultivated tumor cells, and, thus may lead to an improved understanding of the therapeutic options for patients that have already undergone irradiation.

Differences in tumor stroma derived from irradiated versus non-irradiated fibroblasts in a co-culture model with head and neck squamous cell carcinoma